This invention relates to a process of preparing biotin by the reduction of dehydrobiotin. Biotin, vitamin H, is a natural product found largely in the kidney, liver, egg yolk, milk and yeast. The compound is used to prevent symptoms of egg-white injury in experimental animals. Its prime medical use is in various dematitides.
Biotin has been prepared synthetically by Harris et al. (Science, 97, 447 (1943) and Baker et al. (J. Org. Chem., 12, 167 (1947), among others. None of these syntheses, however, were commercially feasible. The first commercial synthesis of biotin resulted from the work of Goldberg and Sternbach (U.S. Pat. Nos. 2,489, 2,489,235 and 2,489,236).
Safir et al., in an article entitled "A Synthesis of d,1-Dehydrobiotin" (J. Org. Chem. 12, 475 (1947), disclose the preparation of a compound believed to be 2-(.delta.-carboxybutyl)-3-amino-4-ketothiophane starting from 7-carbethoxy-2-heptenoic acid. The ketothiophane is subsequently treated with potassium cyanate to yield a product having a melting point of 175.degree.-176.degree. C. The authors assumed this product to be dehydrobiotin. The subsequent reduction of this product to biotin is not illustrated in the article.
It has now been discovered that the Safir et al. process does not result in the formation of 2-(.delta.-carboxybutyl)-3-amino-4-ketothiophane. Furthermore, the compound treated with potassium cyanate (according to Safir et al.) results in a product other than dehydrobiotin, as will be pointed out hereinafter.